Semaglutide reduces antipsychotic-induced weight gain by up to 12.25 kg in inpatients with severe mental illness
Background
Antipsychotic medications, crucial for managing severe mental illnesses (SMI), frequently induce significant weight gain (AIWG) and metabolic dysregulation, including type 2 diabetes (T2D) and dyslipidemia. This metabolic burden exacerbates cardiovascular risk and can impact treatment adherence. While metformin is a recommended first-line intervention for AIWG, clear alternatives for non-responders are lacking. Semaglutide, a GLP-1 receptor agonist, offers a promising mechanism for weight management and metabolic improvement, but its efficacy and safety specifically within the SMI inpatient population remain underexplored.
Study Design
Researchers conducted a retrospective chart review of 47 inpatients with severe mental illness (SMI) receiving antipsychotics at the Centre for Addiction and Mental Health in Toronto. Patients were initiated on once-weekly subcutaneous semaglutide between January 2018 and March 2024, with a maximum dose of 2 mg/week. The study analyzed changes in weight, various metabolic parameters (e.g., BMI, HbA1c, lipid profiles), and documented any reported side effects. This design aimed to evaluate real-world effectiveness and tolerability in a challenging clinical population.
Results
The study included 47 individuals with SMI (mean age 43 ± 13.2 years), of whom 83% had dysglycemia and 66% had T2D at baseline. Significant and sustained weight loss was observed across the cohort. At 3 months, mean weight loss was 3.15 ± 0.77 kg (n=47). This progressed to 7.27 ± 0.97 kg (n=24) at 6 months, 9.33 ± 1.16 kg (n=15) at 9 months, and peaked at 12.25 ± 1.32 kg (n=11) at 12 months (all P < .001). Individuals without T2D experienced greater weight loss compared to those with T2D (P = .022). Additionally, significant decreases were noted in body mass index and HbA1c (P < .001), alongside improvements in lipid parameters.
The mean weight loss reached 12.25 kg at 12 months, demonstrating substantial efficacy for semaglutide in this population. Most common side effects were gastrointestinal in nature, but notably, none resulted in semaglutide discontinuation, indicating good tolerability.
Key Findings
- Semaglutide led to a mean weight loss of 3.15 kg at 3 months (n=47) in inpatients with SMI.
- Mean weight loss reached 12.25 kg at 12 months (n=11) in the semaglutide-treated cohort.
- Significant reductions in
BMIandHbA1c(P < .001) were observed alongside improved lipid parameters. - Individuals without type 2 diabetes experienced greater weight loss versus those with T2D (P = .022).
- Gastrointestinal side effects were common but did not lead to semaglutide discontinuation.
Why It Matters
This study provides crucial real-world evidence supporting semaglutide as an effective and well-tolerated option for managing antipsychotic-induced weight gain (AIWG) and associated metabolic dysfunction in inpatients with severe mental illness (SMI). For clinicians, this offers a valuable alternative when standard interventions like metformin prove insufficient or contraindicated, potentially improving long-term adherence to essential antipsychotic regimens. The observed sustained weight loss and metabolic improvements suggest a viable protocol for integrating GLP-1 receptor agonists into the care of this vulnerable population. While further research is needed, these findings suggest that semaglutide can be safely initiated and maintained in a controlled inpatient setting, addressing a significant unmet clinical need.
semaglutide
antipsychotic-induced weight gain
severe mental illness
metabolic dysregulation
type 2 diabetes
glp-1 agonist